Structral Modulation Of Gut Microbiota In A Non-Alcoholic Fatty Liver Disease Rat Model During Treatment With A Chinese Herbal Formula (Qushi Huayu Fang)

Non-alcoholic fatty liver disease (NAFLD), referring to a wide spectrum of liver damages, has become the major cause of chronic liver diseases in many countries. Accumulating evidence indicates disruption of the gut microbiota by a high-fat diet (HFD) may play a pivotal role in the progression of metabolic disorders such as NAFLD.Here, we analyzed the structural changes of gut microbiota in a HFD-induced NAFLD rat model during treatment with a modernized version of an ancient Chinese herbal formula (CHF), Qushi Huayu Fang, widely used in clinical practice. CHF treatment significantly reduced body weight, alleviated hepatic steatosis, and decreased liver contents of triglycerides and free fatty acids, compared to their HFD-fed counterparts. Gut microbiota of treated and control rats were profiled with polymerase chain reaction denaturing gradient gel electrophoresis and bar-coded pyrosequencing of the V3 region of 16S rRNA genes. Both analyses indicated that CHF significantly shifted the composition of gut microbiota in model rats. Partial least square discriminant analysis and taxonomy-based analysis were further employed to identify key phylotypes responding to HFD and CHF treatment. Most notably, genera Escherichia/Shigella, containing opportunistic pathogens, were significantly enriched in HFD-fed rats compared to controls fed normal chow (P=0.028) but decreased to control levels after CHF treatment. Collinsella, a genus with short chain fatty acid producers, was significantly elevated in CHF-treated rats compared to HFD-fed rats (P=0.015). Short chain fatty acids are essential for epithelium to maintain their normal functions. Our research shows this CHF could change the HFD-disrupted gut microbiota to a healthier state by reducing the abundance of opportunistic pathogens and increasing potentially beneficial bacteria.To explore the potential relationship between gut microbiota and host's health, we employed partial least square regression analysis. Results showed that the gut microbiota data could accurately predict the serum concentration of adiponectin (R=0.77, P<0.0001), indicating that the change in gut microbiota was closely related to adiponection, one of the indicators of host's inflammation, and may contribute to the alleviation of NAFLD. Our work also provides a solid foundation for further research on the interaction of Traditional Chinese Medicine and gut microbiota.